The broad objective of this research proposal is to seek a better understanding, at the molecular level, of the biochemical events which may be associated with the pathogenesis of emphysema, and thus provide a rational basis for the design of drugs that can be used for the effective treatment of this disease. Particular emphasis will be placed on the interaction of the alpha 1-trypsin inhibitor with proteinases which may be responsible for the destruction of lung tissue. This problem will be approached along the following lines: 1) The purification and detailed physicochemical characterization of the alpha 1-trypsin inhibitor of human blood serum; 2) The purification and detailed characterization of leucocyte proteinases capable of digesting lung tissue. Special effort will be devoted to the design of synthetic inhibitors of these enzymes; 3) A study of the mechanism of interaction of alpha 1-trypsin inhibitor with leucocyte proteinases with special emphasis on the chemical nature of the proteinase binding site of the inhibitor.